The film begins with text, saying that in 2012 the US economy collapsed. Corporations took over prisons, and for entertainment they started to film prisoners fight to the death and broadcast it on the internet. Soon, the public wanted more, and so Death Race was invented, being broadcasted on television. Next, we see a Death Race in progress. Frankenstein (David Carradine) and his navigator Case (Natalie Martinez) try to get away from Machine Gun Joe (Tyrese Gibson), who is spraying their car full of bullets. Joe’s navigator is already dead. Another driver is also in the race, but he is shot to death by Joe, who then crashes into his car and causes it to flip in the air. Frankenstein tells Case to activate their defensive weapons, but none of them work. Frankenstein has Case release their back shield, which hits Joe’s car. They are now growing close to the final stretch of the race. Frankenstein says that they’re going to make it, but Case says that since their tank is now exposed, Joe is going to blow them away. Case ejects herself out of the car, and she parachutes safely to the ground. Joe blows up Frankenstein’s car with an RPG before he can reach the finish line.

During the opening credits, we see Jensen Aimes (Jason Statham) working at a steel mill factory. It’s the last day before the factory closes for good, and so all the workers are laid off. Jensen tells some of his friends that he heard about some jobs being available at the docks. They go outside and wait in line to collect their paychecks. They tax Jensen for requesting cash instead of a check. Shortly afterwards, SWAT vans arrive at the factory and cops in riot gear line up. The workers grow violent, and so the SWAT teams fire rubber bullets into the crowd. Jensen and his friends are shot down. That night, Jensen arrives home and kisses his wife Suzy (Janaya Stephens) hello. She’s in the kitchen making dinner, and he hands her the three hundred dollars he got that day. They passionately kiss each other and get ready to have sex on the counter when they hear their baby girl crying on a baby monitor. Jensen says that he’ll calm her down, and tells his daughter a bedtime story. Suzy remains in the kitchen to finish making dinner, and suddenly a masked man appears behind her. After washing himself, Jensen goes to the kitchen and finds Suzy on the floor. He turns around and is sprayed in the face with something by the masked man. When he wakes up, he sees that his wife has been stabbed to death and the bloody knife is planted in his hands. Cops arrive at his house and arrest him for Suzy’s murder. While being handcuffed, Jensen sees the masked man make a gun signal to him with his fingers, and then he escapes.

Six months later  Jensen arrives at an island prison via bus. The bridge is the only way on or off the island. Jensen has his mug shots taken, showing off his tattoos, and then he is hosed down by guard Ulrich (Jason Clarke), who has another guard beat him up. Jensen is escorted to his cell while warden Hennessey (Joan Allen) watches from a catwalk. The next day, we see Hennessey walk around her prison. She is greeted by all the prisoners, including Grimm (Robert LaSardo). Meanwhile, Jensen goes to the cafeteria to eat some slop. Coach (Ian McShane), Gunner (Jacob Vargas), and Lists (Frederick Koehler) all notice Jensen since he’s the new prisoner. Lists recognizes him as an ex-professional driver, but Jensen got arrested a while back and it ruined his career. Coach sees a couple of prisoners group around Jensen, and remarks that he better be as fast off the track as he is on it. A prisoner walks over to Jensen and spits in his oatmeal. Pachenko (Max Ryan) shows up and says that he knows Jensen is a wife killer. He calls him weak for killing women, but then Jensen beats the crap out of Pachenko and his gang with his lunch tray. The fight is quickly broken up by the guards, and they bring Jensen to see Hennessey.

Hennessey sees the cafeteria fight via security footage, and reviews Jensen’s file. She says that he won’t last very long in prison on his own, and so she offers a proposition. She invented Death Race, and it is incredibly popular entertainment. The crowd favorite is Frankenstein, and they are eagerly awaiting his return to the race. However, in the last race he died on the operating table due to his car being blown up by Machine Gun Joe. The public doesn’t know that he’s dead, and since Hennessey doesn’t want to lose the fan favorite she asks Jensen to race as Frankenstein. No one knows what Frankenstein looks like, since his skin was horribly burned and he wore a mask while racing. Jensen declines. Hennessey sweetens the deal by saying that the prisoners who participate in Death Race have to win five races, and if they win they will be granted freedom. Frankenstein has won four races, and if Jensen races as him she’ll allow his four to count as Jensen’s (basically all he needs to do is win this one race and he’ll be freed). Jensen finally agrees to do it, and he is sent to a warehouse in the prison where the prisoners work on their cars in their separate garages. Jensen is introduced to Coach, Gunner, and Lists. Since he’s on their team, they know that he’s not really Frankenstein. Only his crew and a handful of the guards know the truth. Coach introduces Jensen to Frankenstein’s mustang, named The Monster. It’s heavily armored, has machine guns on the front, and has a big steel shield on the back (called the Tombstone). All the cars are equipped with various machine guns for offense, and for defense they have napalm, oil, and smoke. Jensen asks why they can’t just use the cars to escape from the prison. It turns out that they only get the ammo for the cars on the day of the race, and they can only be activated while on the track. Hennessey also has electric kill switches on all the cars, so if they try to use their guns against her and the guards she’ll simply disable the guns. Jensen notices that a huge part of the warehouse has been closed off, but no one knows what the guards are building on the other side.

While in the courtyard, Lists points out to Jensen who some of the other drivers are: 14K (Robin Shu), Grimm, ex-Nascar driver Travis Colt (Justin Mader), Pachenko, and Machine Gun Joe. They are all murderers (both on and off the track), and each car comes with a navigator. All the navigators are female for ratings; the only exception is Machine Gun Joe, who uses guy navigators (which makes everyone think that he’s gay). Joe also has a history of his navigators being killed, and so he scars his own face each time one of them dies. Joe comes up to Jensen and calls him Igor for being the ugliest person he’s ever seen. Coach says that Jensen is Frankenstein’s new grease monkey, and Joe promises that he will kill Frankenstein this time. Jensen also sees some male prisoners being transferred from somewhere else to work on the track. The other prisoners have metal devices strapped to their wrists so that they can be monitored and won’t try to swim away. The day comes for the first leg of Death Race. Jensen puts on Frankenstein’s outfit and mask. As Jensen is led out to the track, the prisoners chant Frankenstein’s name. Jensen meets up with his crew and climbs into the Monster. The women’s prison bus arrives and it of course gets everyone riled up. All the female navigators get off the bus and go to their cars. Case goes to the Monster and gets in. She also knows that Jensen is not the real Frankenstein, but will remain silent. Joe walks over and says that the race is between him and Frankenstein, and he’ll take him out. Coach and the crew put the bullet-proof glass on the Monster, and Coach tells Jensen that he can take off the mask while in the car since the glass is also reflective (no one can see inside the car). He also tells him to concentrate on taking out the other drivers during the first two legs of the race. Jensen takes off his mask, and Case tells him that he’s a lot better looking than Frankenstein. Case also mentions that she’s in prison for killing her husband, who happened to be a police officer. All the drivers move their cars onto the track, and Hennessey starts up the television broadcast. She charges $99 dollars for the viewers to see one leg of the race, or they can pay $250 to see all three legs of the race. On the track are three plates which will be activated after the first lap. The shield plate activates the defensive weapons. The sword plate activates the offensive weapons. The skull plate activates some huge spikes to pop up from the ground a short distance away.

The light goes green, and the drivers are off. Almost immediately Pachenko, Joe, and 14K gang up on Jensen. After the first lap, all the plates are activated. Joe runs over a sword plate and shoots up the competition. During the race, Case tells Jensen where to go for shortcuts and he winds up in front. Joe targets Jensen and shoots the hell out of the Tombstone. Travis gets a sword plate and also shoots up Jensen’s car while they go through a warehouse. Jensen runs over a shield plate, but Case says that nothing works. Coach tells Jensen to either lose or kill Travis. Jensen has Case sit on his lap and place a canister of oil on her seat. He ejects her seat, which causes it to hit the ceiling, busting the canister and spraying Travis’ car with the oil. Case then throws the cigarette lighter at Travis’ car, burning him alive along with his navigator. Joe rams into Travis’ car, causing him to flip in the air and explode. Joe continues to try to kill Jensen, and accidentally kills some prisoners watching from the sidelines. Coach saves Lists and Gunner from being shot. Grimm activates a skull plate and the spikes pop up on the track, impaling a driver and his navigator. The spikes also crush the car, causing it to explode. Grimm gets a sword plate and fires on Joe, causing his car to stall. Grimm fires on another car, but causes the other car to release some spikes from the back. Grimm runs over the spikes, spins out of control, and is then blown up by 14K, which causes his car to flip into a section of a wall. Grimm stumbles out of the car, bloodied and still alive. He looks to the cameras and says that they can do whatever they want to him, but they can’t kill him. Joe then comes around the corner and hits Grimm with his car, annihilating him. Jensen and Pachenko wind up neck-to-neck while racing, and then Pachenko makes a gun signal with his fingers. Jensen gets distracted by this and is then hit by Joe, causing his car to stall. The leg of the race is over, and Jensen winds up in last place.

The remaining drivers go back to their garages to repair their cars, and the female navigators go back on the bus. While inspecting the car, Gunner sees that the defensive parts of the Monster work just fine, and which causes all of them to get suspicious of Case. At night, Jensen thinks back to Suzy’s murder and he realizes that Pachenko killed his wife (since he used the gun signal and the masked man also had one of the metal wrist guards on). Jensen sees Hennessey and tells her that he refuses to race in the next leg, while also making it clear that he knows she had his wife killed so that he would get sent to the prison and participate in Death Race. Hennessey has her guards uncuff Jensen and then leave him alone with her. She takes out a picture of a happy couple with a baby, and tells Jensen that they are his daughter’s new parents. If he wins the race, she’ll tell him where his daughter is. Jensen leans over to threaten Hennessey, but we see that she has a shotgun aimed at his leg underneath her desk. Instead, he takes the picture to keep. In the courtyard, Jensen looks at a picture of his daughter. Coach walks up and says that he knows Jensen’s not a killer. Jensen asks him why he doesn’t have an inmate number. Coach says that he was put up for parole three years ago, but when it was his time to leave the prison he found that he couldn’t. The world has changed so much outside that he would rather remain in prison where he knows everything. Jensen tells Coach that Hennessey was responsible for his wife’s death.

Later on, Jensen is working on the Monster when Lists tells him that he ought to rest before the next leg. Jensen refuses, but then he sees Pachenko walking to his garage. Jensen says that he’s going to take a break and follows Pachenko while Lists watches. Jensen goes to Pachenko’s garage, and is jumped by his crew. While Jensen is being strangled with a chain by a goon, Pachenko beats him up. He grabs a big wrench and says that he’s going to cut off Jensen’s head when he suddenly stops. He turns around and we see that Lists has stabbed him in the back with a pen. Lists tries to run away, but is hit in the leg with a pipe and Pachenko steps on his hand. Jensen breaks free by grabbing a shard of metal and stabbing the guy strangling him in the leg. He then goes on a rampage, beating the crap out of Pachenko’s crew. He eventually gets to Pachenko and thrashes him all over the garage. Before he can kill him though, they are both shot with tasers by Ulrich and his guards. Ulrich tells them to save it for the race. The day comes for the second leg of Death Race. Pachenko again makes a gun gesture with his hands and aims at Jensen. All the remaining drivers (Jensen, Pachenko, Joe, 14K, and two others) drive out onto the track. The light goes green, and the drivers are off…except for Jensen. Instead of racing, he drives at a leisurely pace and goes through a warehouse to talk with Case. He threatens to eject her from the car and have her busted on the ceiling of the warehouse if she isn’t straight with him. It turns out that Case sabotaged Frankenstein before he died, and she also sabotaged Jensen in the first leg of the race. Hennessey made her do this by offering her release papers. She doesn’t want him to win, and is planning on keeping him in the prison to continue to race as Frankenstein in the future. After the truth comes out, Jensen gets back into the race.

Jensen aims solely on Pachenko while driving. Pachenko gets a sword plate and fires on Jensen in front of him. Coach tells Jensen to grab the next shield plate, but he instead gets a sword plate. Jensen then spins his car around and fires upon Pachenko while driving backwards. Jensen runs over a shield plate, and has Case use the smoke on Pachenko, causing him to crash his car against a pillar. Jensen stops the Monster in the middle of the track and allows the other drivers to pass him by. Pachenko, bloodied, crawls out of his wreckage and is hit by Jensen’s door as he goes in reverse. Case tells him that in races they don’t stop or get out of the car. Jensen ignores her and puts on Frankenstein’s mask. He gets out of the Monster and walks over to Pachenko, who says that Hennessey made him do it. Regardless, Jensen snaps Pachenko’s neck, killing him. He then looks up at a video camera and stares angrily at it, causing Hennessey to get uneasy. Joe’s navigator learns that Frankenstein is out of his car, and so Joe runs over a shield plate to use. However, Hennessey has the plate deactivated because she doesn’t want Jensen to be killed yet. Joe gets pissed and kicks his navigator out of his car, causing him to break his back on a concrete pillar. He then drives back to his crew and they shove an unlucky guy into the car to act as the new navigator. Hennessey releases what the guards have been building in their section of the warehouse  the Dreadnought, a heavily armored truck/tank. It has massive machine guns, rockets, flamethrowers, and guards manning all the weapons. The Dreadnought attacks all the drivers, blowing up two. While going through a warehouse, the Dreadnought attacks 14K. Spinning spikes on the side of the wheels jam into 14K’s car, killing his navigator and splattering her blood all over the inside. His car is then snagged onto the back of the Dreadnought, and he is blown up by the tank. Jensen and Joe are the last two racers alive. Jensen has Lists patch his radio to Joe’s, and he gets him to team up with him against the Dreadnought. They drive on opposite sides of the tank and are fired upon by the guards. Joe’s driver is shot to death by machine guns. Jensen and Joe drive to the front of the Dreadnought and then drive over a skull plate. Spikes pop up from the ground and impale the Dreadnought, causing it to crash and explode.

After the leg of the race is over, all the prisoners cheer Frankenstein and Joe as they are escorted back to their cells. While the remaining crews repair the cars, Joe walks over to Jensen’s garage and tells him that he must be close with Frankenstein. Since he notices that they sound alike, he wonders if hurting Jensen would affect Frankenstein’s racing. Jensen says that it won’t, and Joe leaves. Meanwhile, Hennessey and Ulrich plot to kill Jensen on the track. While Hennessey rounds up the prisoners in the courtyard for a speech, Ulrich plants a C4 bomb underneath the Monster. Jensen tells Coach that no one will ever win and be released from the prison. When they go back to the garage, Coach shows Jensen a video playback of Grimm’s death. He specifically points out something in the background to Jensen, who acknowledges it. Jensen walks over to Joe’s garage, where Joe says that he’s won three races so far, and he’s determined to win two more because he wants out. Jensen tells him that he should talk to Frankenstein before the race. Before the last leg of the race, Hennessey goes to talk with Jensen while he suits up. She gives him his signed release papers, hoping it will inspire him to win. Jensen and Joe drive onto the track for the last leg, and Joe gets a new navigator. Case sees that Jensen’s crew has put an extra half tank of gas in the back. Jensen tells her that it’ll come in handy later on.

The lights go green, and Jensen & Joe speed off. Jensen runs over a sword plate, but Hennessey has it deactivated. She then has it reactivated so that Joe can get it. Joe fires upon Jensen, and the Tombstone takes the brunt of the damage. Jensen drives over a shield plate, but Hennessey has it deactivated and then reactivates it for Joe. Joe fires at Jensen with RPGs, and Coach tells them to lose the Tombstone. Case detaches it, but Joe swerves out of the way since he learned his lesson last time. So that they won’t lose viewers, Hennessey allows Jensen to run over an activated shield plate. While driving, both drivers come upon the area where Grimm was killed. Joe fires his RPGs at Jensen, but they blow up the half-destroyed wall instead. Joe and Jensen then together drive through the wall and make their way to the bridge. The half-destroyed wall is what Coach showed Jensen earlier. Jensen and Joe compliment each other for putting up a good show for the warden as they drive towards freedom. Coach wishes Jensen good luck on the outside. Hennessey uses the kill switch to disable the weapons on the cars and shuts down the broadcast of Death Race. Loads of cops get into their cars and try to prevent them from driving past the bridge. Jensen has Case eject the half tank of gas out the back of the Monster. The tank explodes when a cop crashes into it, and it causes the other cops behind him to get caught up in the explosion and wreckage. Guards at the gate make a last attempt to prevent the escape by shooting at the cars. Joe’s navigator is shot to death, but both cars make it past the gate. Hennessey, extremely pissed off, presses the detonator for the bomb underneath the Monster, but nothing happens. It turns out Coach, Gunner, and Lists found the bomb under the car and disarmed it before removing it.

Hennessey has helicopters follow Jensen and Joe, firing at them with machine guns. Jensen and Joe break off and go in different directions. Hennessey has the helicopters follow the Monster. Jensen asks Case if she’s okay with what they’re about to do next. Case says that she is, since Hennessey already gave her signed release papers too and she owes it to both him and Frankenstein. While going under a dark spot, Jensen jumps out of the car. Case drives the Monster and leads the cops away from Jensen, who remains unseen by the helicopters. The helicopters eventually cause a huge explosion in front of the Monster, causing Case to stop. She puts on Frankenstein’s outfit and wears the mask. Case then steps out of the car and surrenders as Jensen watches from afar. Joe shows up after ditching his car, and he jumps onto a train with Jensen. Joe also brought a bag with Hawaiian shirts so that they can ditch their prison outfits. Jensen asks where Joe’s heading. He says that he’s going to Miami, and Jensen says that he’ll meet up with him there. But first he has to get his baby daughter back. They both remark that it’s a shame neither of them got to kill Hennessey. Speaking of which, back at the prison, Ulrich says that the broadcast has been favorable despite the escape and gifts are already being sent in. He hands her a box, and she opens it. Inside is the C4 bomb that they planted on the Monster. Coach detonates it, killing both Hennessey and Ulrich. He then turns to the camera and says “I love this game”.

Some time later  we see Jensen and Joe in Mexico. They are working on an old car when a fancy car drives up to them. Case gets out, a freed woman and looking better than ever. Jensen introduces Case to his daughter, and the film ends with all of them looking at Case’s car, which she won in a card game.